Peripheral T cell responses to tumour antigens are associated with molecular, immunogenetic and cellular features of breast cancer patients.

Abstract:

PURPOSE:Breast cancer is a leading cause of cancer deaths in women, but despite steady improvements in therapies, treatment is still suboptimal. Immunotherapy holds promise as a more effective therapy for breast cancer; supporting this, our prior study showed that patients possessing HER2-reactive CD8+ T cells in blood experience survival superior to patients without these cells. Here, we define a composite set of biomarkers that identify patients with T cell responses to tumour antigens. METHODS:We assessed T cell responses following in vitro stimulation with the HER2, MUC1 and SUR tumour-associated antigens (TAA) by flow cytometry and intracellular cytokine staining in 50 breast cancer patients. We also measured HLA type, serum cytokines, tumour-infiltrating leukocytes and blood leukocyte populations. RESULTS:We found few correlations between TAA-reactive T cells and HLA type, serum cytokines and tumour-infiltrating leukocytes, whereas blood leukocyte phenotypes broadly correlated with TAA responses. This showed monocytes, natural killer cells, dendritic cells and T cells to be inversely associated with both CD4+ and CD8+ T cells reactive to tumour antigens. Moreover, combining multiple parameters improved the accuracy in predicting patients with TAA-responsive T cells. CONCLUSION:This study therefore defines composite immune profiles that identify patients responding to TAAs which may allow better personalisation of cancer therapies.

authors

Janssen N,Fortis SP,Speigl L,Haritos C,Sotiriadou NN,Sofopoulos M,Arnogiannaki N,Stavropoulos-Giokas C,Dinou A,Perez S,Pawelec G,Baxevanis CN,Shipp C

doi

10.1007/s10549-016-4037-z

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

51-62

issue

1

eissn

0167-6806

issn

1573-7217

pii

10.1007/s10549-016-4037-z

journal_volume

161

pub_type

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